chr17-5428576-A-C

Variant names:

• chr17-5428576-A-C
• rs8070740
• NM_001033002.4:c.630+365A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001160243.2(RPAIN):​c.*299A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000104 in 963,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: RPAIN NM_001160243.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

Genes affected

RPAIN (HGNC:28641): (RPA interacting protein) Predicted to enable metal ion binding activity. Acts upstream of or within several processes, including DNA metabolic process; protein import into nucleus; and response to UV. Located in PML body; cytoplasm; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263272 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160243.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAIN	NM_001033002.4	MANE Select	c.630+365A>C		intron	N/A	NP_001028174.2	Q86UA6-1
	RPAIN	NM_001160243.2		c.*299A>C		3_prime_UTR	Exon 6 of 6	NP_001153715.1	Q86UA6-8
	RPAIN	NM_001160244.2		c.489+2277A>C		intron	N/A	NP_001153716.1	Q86UA6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAIN	ENST00000381209.8	TSL:1 MANE Select	c.630+365A>C		intron	N/A	ENSP00000370606.3	Q86UA6-1
	RPAIN	ENST00000381208.9	TSL:1	c.489+2277A>C		intron	N/A	ENSP00000370605.5	Q86UA6-2
	RPAIN	ENST00000536255.6	TSL:1	c.314-3966A>C		intron	N/A	ENSP00000439939.2	Q86UA6-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000104 AC: 1 AN: 963740 Hom.: 0 Cov.: 13 AF XY: 0.00000215 AC XY: 1 AN XY: 464400

African (AFR) AF: 0.00 AC: 0 AN: 21258

American (AMR) AF: 0.00 AC: 0 AN: 11710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11790

East Asian (EAS) AF: 0.00 AC: 0 AN: 17380

South Asian (SAS) AF: 0.0000202 AC: 1 AN: 49604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2434

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 800328

Other (OTH) AF: 0.00 AC: 0 AN: 37188

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8070740; hg19: chr17-5331896;